EP0320727B1 - Verfahren zur Herstellung von Cysteamin-Säureadditionssalzen - Google Patents

Verfahren zur Herstellung von Cysteamin-Säureadditionssalzen Download PDF

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Publication number
EP0320727B1
EP0320727B1 EP88120207A EP88120207A EP0320727B1 EP 0320727 B1 EP0320727 B1 EP 0320727B1 EP 88120207 A EP88120207 A EP 88120207A EP 88120207 A EP88120207 A EP 88120207A EP 0320727 B1 EP0320727 B1 EP 0320727B1
Authority
EP
European Patent Office
Prior art keywords
acid
aziridine
ketone
addition
hydrogen sulfide
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
EP88120207A
Other languages
German (de)
English (en)
French (fr)
Other versions
EP0320727A3 (en
EP0320727A2 (de
Inventor
Andreas Dr. Hohmann
Wolfgang Dr. Reuther
Rolf Dr. Fikentscher
Theo Dr. Proll
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
BASF SE
Original Assignee
BASF SE
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Filing date
Publication date
Application filed by BASF SE filed Critical BASF SE
Publication of EP0320727A2 publication Critical patent/EP0320727A2/de
Publication of EP0320727A3 publication Critical patent/EP0320727A3/de
Application granted granted Critical
Publication of EP0320727B1 publication Critical patent/EP0320727B1/de
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
    • C07C319/02—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of thiols
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
    • C07C323/24—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C323/25—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated

Definitions

  • the present invention relates to a new process for the preparation of cysteamine acid addition salts by reacting aziridine with an inorganic sulfur compound of oxidation state -2 and with a ketone and subsequent acidic hydrolysis of the thiazolidine formed as an intermediate, whereby aziridine and the ketone with ammonium hydrogen sulfide or a metal hydrogen sulfide with the addition of a medium to strong acid at a pH value that is greater than or equal to 8.5.
  • DE-A-3 025 461 discloses reacting 2-aminoethyl hydrogen sulfate with a ketone to form a thiazolidine derivative and then converting this to an acid addition salt of cysteamine by acid hydrolysis.
  • this process is very complex since the thiazolidine formation takes place partly in an autoclave and the resulting thiazolidine must in all cases be purified by distillation after it has been worked up.
  • the sulfuric acid half-ester of 2-aminoethanol is to be prepared in an additional precursor.
  • JP-A-39 414/1973 describes the reaction of aziridine with a ketone and hydrogen sulfide to give a thiazolidine derivative, which is then converted into an acid addition salt of cysteamine by acid hydrolysis.
  • the synthetic route to the thiazolidine derivative described there is also from Ann. Chem. Volume 566, pp. 210 f., 1950, and DE-A-747 733.
  • the disadvantage of this process is the use of hydrogen sulfide. Due to the high toxicity of hydrogen sulfide, a high level of safety is required when using it.
  • R1 and R2 in formula I mean, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, hexyl or 2-methylpentyl.
  • R1 and R2 together represent C4-C6-alkylene, for example tetramethylene, pentamethylene, hexamethylene, 2-methyltetramethylene or 2- or 3-methylpentamethylene may be mentioned as the remainder.
  • Acetone, methyl ethyl ketone or cyclohexanone is preferably used as the ketone of the formula I.
  • the metal hydrogen sulfides to be used in the process according to the invention are, for example, alkali metal or alkaline earth metal hydrogen sulfides, such as lithium, sodium, potassium, magnesium or calcium hydrogen sulfide.
  • Ammonium hydrogen sulfide or an alkali hydrogen sulfide is preferably used.
  • Sodium or potassium hydrogen sulfide is particularly preferred.
  • Those acids whose pK a value is less than or equal to 3.5 are generally to be regarded as medium-strong to strong acids in the sense according to the invention. In general, the pK a value is -10 to +3.5.
  • both inorganic and organic acids can be used if their pKa value meets the above requirement.
  • acids examples include hydrochloric acid, hydrobromic acid, hydrofluoric acid, sulfuric acid, nitric acid, phosphoric acid, trifluoroacetic acid, trichloroacetic acid, methanesulfonic acid, benzenesulfonic acid or p-toluenesulfonic acid.
  • a strong inorganic acid is preferably used.
  • the use of hydrochloric acid is particularly preferred.
  • the process according to the invention which can be carried out either continuously or batchwise, is expediently carried out in such a way that the ketone I and the respective hydrogen sulfide, which is advantageously used in the form of a 10 to 70% strength by weight aqueous solution, and adds aziridine and the medium to strong acid to this mixture.
  • the addition of aziridine and acid can be delayed, i.e. first the addition of aziridine and then the addition of the acid, or preferably simultaneously, but spatially separated from one another. It is also possible to add aziridine and acid in portions in alternating order.
  • the reaction is preferably carried out under atmospheric pressure or else under slightly elevated pressure (up to about 2 bar) and can be carried out with or without protective gas. It is preferable to work in the presence of a protective gas.
  • the protective gas comes e.g. Nitrogen or helium.
  • the time required for the addition of aziridine and acid is generally 0.5 to 5 hours, preferably 1 to 2 hours.
  • the reaction temperature is -10 to + 100 ° C, preferably 0 to 60 ° C and in particular 20 to 40 ° C.
  • the acid which is expedient is the same acid which is added during the reaction of the aziridine. It is also possible to use another acid for hydrolysis. In this case, the choice of acid depends primarily on which cysteamine acid addition salt is intended at the end. The use of hydrochloric acid is also preferred here.
  • the hydrolysis is complete after a reaction time of 0.5 to 4 hours.
  • the solution of the cysteamine acid addition salt obtained is cooled and requires no further purification. It is now possible to remove the water from the cysteamine salt or to process it directly in solution. In some cases it may also be advantageous to treat the aqueous solution of the cysteamine acid addition salt with activated carbon.
  • Cysteamine hydrochloride is a valuable intermediate for the production of the H2 blockers cimetidine and ranitidine.
  • the solution was heated and ethyl methyl ketone / water was distilled off to a transition temperature of 100 ° C.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
EP88120207A 1987-12-12 1988-12-03 Verfahren zur Herstellung von Cysteamin-Säureadditionssalzen Expired - Lifetime EP0320727B1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE3742265 1987-12-12
DE19873742265 DE3742265A1 (de) 1987-12-12 1987-12-12 Verfahren zur herstellung von cysteamin-saeureadditionssalzen

Publications (3)

Publication Number Publication Date
EP0320727A2 EP0320727A2 (de) 1989-06-21
EP0320727A3 EP0320727A3 (en) 1989-10-04
EP0320727B1 true EP0320727B1 (de) 1992-01-02

Family

ID=6342525

Family Applications (1)

Application Number Title Priority Date Filing Date
EP88120207A Expired - Lifetime EP0320727B1 (de) 1987-12-12 1988-12-03 Verfahren zur Herstellung von Cysteamin-Säureadditionssalzen

Country Status (5)

Country Link
US (1) US5017725A (ko)
EP (1) EP0320727B1 (ko)
JP (1) JP2545454B2 (ko)
KR (1) KR960008110B1 (ko)
DE (2) DE3742265A1 (ko)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HU208115B (en) * 1989-10-03 1993-08-30 Biochemie Gmbh New process for producting pleuromutilin derivatives
EP4457210A2 (en) 2021-12-27 2024-11-06 Recordati Industria Chimica E Farmaceutica SPA Process for the preparation of cysteamine bitartrate and product so obtained

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE747733C (de) * 1939-03-31 1944-10-11 Verfahren zur Herstellung von Thiazolidinen
US3574698A (en) * 1967-07-19 1971-04-13 Exxon Research Engineering Co Preparation of salts of 2-mercaptoethylamines and their s-acyl analogs
JPS5441569B2 (ko) * 1971-09-30 1979-12-08
IE49614B1 (en) * 1979-07-04 1985-10-30 Sogo Pharm Process for preparing mineral acid salt of cysteamines
JPS5681574A (en) * 1979-12-07 1981-07-03 Sogo Yatsukou Kk Preparation of 2,2-disubstituted thiazolidine
JPS6050186B2 (ja) * 1980-07-15 1985-11-07 三井東圧化学株式会社 ２−メルカプトエチルアミンハロゲン化水素酸塩類の製造法
EP0054409B1 (en) * 1980-12-12 1985-09-18 Fine Organics Limited Preparation of thiazolidine derivatives

Also Published As

Publication number Publication date
DE3867451D1 (de) 1992-02-13
US5017725A (en) 1991-05-21
KR960008110B1 (ko) 1996-06-20
KR890009863A (ko) 1989-08-04
EP0320727A3 (en) 1989-10-04
EP0320727A2 (de) 1989-06-21
DE3742265A1 (de) 1989-06-22
JP2545454B2 (ja) 1996-10-16
JPH01199941A (ja) 1989-08-11

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